Synthesis of 7-oxo-7H-naphtho[1,2,3-de]quinoline derivatives as potential anticancer agents active on multidrug resistant cell lines

Following our earlier finding that tetracyclic anthraquinone analogs with a fused pyridone ring exhibit cytotoxic activity toward multidrug resistant tumor cells, a series of new potential antitumor agents, 7-oxo-7H-naphtho[1,2,3-de]quinoline derivatives (3, 6-8, 10-12, 14, 15, and 18), bearing one or two basic side chains and various substituents at the pyridone ring, have been synthesized. The compounds have been obtained from 1-amino-4-chloroanthraquinone or 1-aminoanthraquinone by cyclization with diethyl malonate and the subsequent reactions of the key intermediates 2, 4, and 17. The compounds exhibited cytotoxic activity toward sensitive human leukemia cell line HL-60 and against its resistant sublines HL-60/VINC (MDR1 type) and HL-60/DX (MRP1 type).